1. Field Of The Invention
The invention relates to a process for the production of 2-substituted 5-chlorimidazole-4-carbaldehydes of the general formula: ##STR2## wherein R is hydrogen, an alkyl group, an alkenyl group, a cycloalkyl group, a benzyl group, a phenyl group or an aryl group. The invention also relates to certain 2-substituted 3,5-dihydroimidazolin-4-ones.
2. Background Art
Several methods for the production of the above-mentioned compounds according to general formula I are known.
U.S. Pat. No. 4,355,040 describes a process according to which 2-amino-3,3-dichloro-acrylonitrile is reacted with an aldehyde to the corresponding azomethine intermediate product and further with a hydrogen halide and water to the 2-substituted 5-haloimidazole-4-carbaldehyde. Experimental data is lacking in the patent. A great drawback of the synthesis is that the 2-amino-3,3-dichloroacrylonitrile used first has to be produced starting from dichloroacetonitrile by its reaction with hydrogen cyanide/sodium cyanide. The extremely toxic reactants and the safety measures associated therewith that are already necessary for the preparation of the initial product, make the entire process unsuitable for industrial-scale production.
U.S. Pat. No. 4,355,040 discloses in another variant a 3-stage process, in which, in a first stage, an amidinehydrochloride is cyclized with high NH.sub.3 pressure with dihydroxyacetone, the imidazole alcohol is halogenated and finally oxidized to the aldehyde.
It has turned out that pressures of over 20 bars are necessary for the cyclization reaction.
The oxidation of the alcohol works according to U.S. Pat. No. 4,355,040 in the presence of chromium oxide. It is obvious that an oxidation with heavy metal oxides, that are not recyclable as a rule, is no longer justifiable from present ecological aspects and requirements.
BROAD DESCRIPTION OF THE INVENTION
The main objective of the invention is to provide processes that do no have the above-mentioned drawbacks of the prior art. The main objective of the invention is achieved by the new process of the invention for the production of 2-substituted 5-chlorimidazoles, and the new 2-substituted 3,5-dihydroimidazol-4-ones of the invention.
Other objectives and advantages of the invention are set out herein or are obvious herefrom to one skilled in the art. The other objectives and advantages of the invention are achieved by the compounds and process of the invention.
The invention involves a process for the production of 2-substituted 5-chlorimidazole-4-carbaldehydes of the general formula: ##STR3## wherein R is hydrogen, an alkyl group, an alkenyl group, a cycloalkyl group, a benzyl group, a phenyl group or an aryl group. The process includes, in the first stage, reacting a glycine ester hydrohalide of the general formula: ##STR4## wherein R.sub.1 is an alkyl group and X is a halogen atom, with an imidic acid ester of the general formula: ##STR5## wherein R has the above-mentioned meaning and R.sub.2 is an alkyl group, in the presence of a base to provide the 2-substituted 3,5-dihydroimidazole-4-one of the general formula: ##STR6## wherein R has the above-mentioned meaning and, in the second stage, is further reacted with phosphoroxy chloride in the presence of N,N-dimethylformamide to the end product.
Preferably an alkali hydroxide or an alkali alcoholate is used as the base in the first stage. Preferably the reaction in the first stage is performed in a pH range between 7 and 12. Preferably the reactants of the first stage, namely, the glycine hydrohalide, the imidic acid ester and the base, are reacted in the stochiometric molar ratio of 1:1:1. Preferably the reaction temperature in the first stage is between -20.degree. and 50.degree. C. Preferably the reactants of the second stage, namely, the 2-substituted 3,5-dihydroimidazol-4-one, the phosphoroxy chloride and the N,N-dimethylformamide, are reacted in a molar ratio of 1:1:1 to 1:5:5. Preferably the reaction temperature in the second stage is betwen 50.degree. and 130.degree. C.
Preferably the 2-substituted 3,5-dihydroimidazol-4-one of the general formula IV is not isolated in the course of the process.
The invention also involves 2-substituted 3,5-dihydroimidazol-4-ones of the general formula IV wherein R is n-propyl, n-butyl, 2-butenyl or 3-butenyl.
The 2-substituted 5-chlorimidazole-4-carbaldehydes of the general formula I are important initial products for the production of antihypertensive pharmaceutical agents (U.S. Pat. No. 4,355,040) or herbicial compounds (German OS 2804435).